Our overall objective is to investigate the molecular mechanism of cataractogenesis due to oxidants in the human, and attempt its prevention. Light microscopic studies suggested that the experimental model of cataract induced in rabbit by feeding the catalase inhibitor, 3-amino-1H-1,2,4-triazole, resembles human senile cortical cataract. We have recently observed increased malondialdehyde (MDA) in human senile cataract and regard this as evidence of lipid peroxidation. It was also noted that H2O2 induced lipid peroxidation in rabbit lens in vitro. We propose to continue studies on lipid peroxidation in cataract both in the human and in the animal model, particularly as related to the role of MDA in crosslinking of lens protein and amino acids by Schiff base conjugates. The mechanism will be examined of oxidative damage to the plasma membrane of lens by O2 minus, H2O2 and OH generated enzymatically in situ by assaying MDA formation, alteration of transport parameters and oxidation of membrane-SH. Transport of cations and amino acids will be studied in relation to cataract by determining fluxes of 86Rb ion, 22Na, and radioactive leucine. We will also assay superoxide dismutase, catalase and glutathione peroxidase in acatalasemic mouse lens. Continued efforts will be made to prevent or arrest cataract in rabbits by using various biological antioxidants.